Fluid transfer device connecting a medicinal vessel and an IV bag in closed system

ABSTRACT

A fluid transfer device connecting a medicinal vessel and an intravenous (IV) bag for enabling the mixing in closed system of the two products contained therein by means of a syringe, comprising a three-way plug valve assembly ( 3 ) with a first port ending in a connector ( 5 ) for a syringe, and a second and a third port ( 8, 7 ), each one provided into a respective spike ( 1, 2 ) connected to a housing ( 16, 17 ) for a container of medicinal product. Within the first one of the said two spikes ( 1 ) a further independent channel ( 13 ) is provided for the inlet and the outlet of air, communicating with the external environment through a hydrophobic filter ( 14 ). The second one of said two spikes ( 2 ) is capable of piercing the rubber closure of the injection point of a bag of medicinal product, and the corresponding housing ( 17 ) consists of two flexible arms ( 18, 19 ) fastenable to each other at the respective ends, so as to be tightened around the tube of the said injection point.

The present invention concerns a fluid transfer device connecting amedicinal vessel and an intravenous (IV) bag in dosed system. Morespecifically, the invention relates to a device provided with athree-way valve, allowing to transfer two pharmaceutical products,respectively from a rigid container such as a bottle or a vial and froma bag-type container, by means of a syringe. The device is used toobtain the mixture of the two products by transfer from one container tothe other, without removing any one of the three elements (i.e., vessel,bag and syringe) from the assembly until the end of the operation.

As it is known, many medicinal products for intravenous administrationare diluted before use in suitably proportioned amounts of injectable orperfusional solutions, in order to be injected or infused to the patientby the intravenous route, i.e. in the phleboclysis form. In some casesthese medicaments are placed on the market in the liquid form, e.g. assolutions or as stable suspensions, while in other cases they are in thedry powder form. Active ingredients in the dry powder form must bereconstituted before use by the addition of a measured amount of liquid.The transfer and the dilution or the reconstitution of the saidmedicinal products before use are conventionally carried out by means ofa syringe provided with needle.

When a medicament to be reconstituted is used, a predetermined amount ofinjectable diluent solution or of perfusional solution is taken by meansof a syringe from the relevant container, and is introduced in thebottle or vial of medicament. The latter is normally provided with apierceable rubber stopper. Once it has been diluted, the drug is takenup from its bottle with the syringe and is administered to the patientintravenously, or it is transferred, wholly or in part, in the containerof the perfusional solution, so as to obtain the desired dosage ofactive ingredient to be infused.

It is evident that the operations referred to above unavoidably involvethe production of splashes and aerosols that diffuse through the airfrom the syringe, for instance when air is expelled from the syringeduring the dosing operation, or when the needle is extracted from thebottle of medicament. In the particularly important case where themedicament is an anticancer drug, the medical personnel coming intocontact with the drug, or breathing it, during the preparation of theintravenous infusion set is exposed to a non negligible risk. Theprolonged and repeated exposure to doses even extremely reduced of suchsubstances may result in long term effects of the same kind as thoseborne by the patients. For some antineoplastic drugs, such as, e.g.,cyclophosphamide, a carcinogenic activity has already been ascertained,while other drugs are still under evaluation in this respect.

Another case where the formation of drug-containing aerosols isparticularly harmful is the case of antibiotics. In this case the activeingredient released in the environment may cause the development ofresistance by the bacterial strains present therein. The foregoing mayeasily result in the development of infections difficult to overcome,specially in the hospital environment.

A further problem involved by the conventional operations of transferand reconstitution of drugs by means of a syringe is the impossibilityof maintaining a complete sterility in the manipulation. Themicro-organisms present in the environment or on the operator's handsmay come into contact with the needle, and from here they may be carriedinto the solution to be infused or injected to the patient. Since thesaid solution is injected directly in the patient's bloodstream, theforegoing involves a remarkable risk of infections, specially in view ofthe weakened conditions of the patient receiving such therapies.

In order to reduce to some extent the occurrence of the first one of theproblems cited above, that is the formation of splashes and aerosols,some devices known as “vented spike” are already available on themarket. Such devices are spikes provided with a hydrophobic filter thatare placed between the syringe (without needle) and the container ofmedicinal product, serving as a port for the inlet and the outlet of airduring the movements of the syringe plunger and, if desired, as a filterfor the liquid transferred. The vented spike devices consist of a hollowspike suitable to perforate the stopper of a pharmaceutical container inthe same way as a syringe, of an aperture for the passage of air,provided with a hydrophobic filter of a porosity suitable to preventboth the passage of aerosol toward the exterior and the passage ofmicro-organisms towards the interior, optionally of a filter placed onthe liquid path and of a connector for a syringe.

Although they actually reduce the production of aerosols, the vented;spike devices do not constitute systems completely isolated from theexterior, as they do not connect both vessels at the same time, andrequire that the device be removed from the first vessel in order totransfer the liquid to the second vessel. Therefore, the risk ofcontamination of the medicament still exists, and the risk that theoperator comes into contact with the drug is still not totally avoided.

The PCT application publ. No. 96/29113, in the name of Medimop MedicalProjects Ltd. et al., discloses a transfer device for medicinal fluidshaving at least three ports, one of which is connected with a syringe(also in this case, without needle). The device is provided with a plugcock, that may be rotated to establish fluid communication between twoof the three ports, in turn. At least one of the three ports is providedwith an adaptor for connection with the upper part of a bottle, saidadaptor having a hollow spike.

In some of its embodiments, the said transfer device is designed toconnect a syringe, previously filled in with diluting solution, a vialof medicament to be reconstituted and, on the third port, directly thepatient to be treated. Other embodiments concern the connection of twomedicinal containers (through the syringe), in order to obtain a closedsystem that allows the blending of two different liquid products throughthe syringe, without removing any one of the three elements up to thecompletion of the operation. Such device, according to the disclosure ofthe document, is designed so as to allow an antiseptic administration ofthe drug, as it prevents any contact of the latter and of the injectableor perfusional solution with the external environment for the wholeblending and dosing operation, up to the administration to the patient.

In the embodiments providing the connection of two vessels, the deviceat issue is endowed with two opposedly placed housings for the head oftwo vials or bottles, each housing being provided with a hollow spike.Between the said two housings there is provided a valve assemblyconsisting of a three-way plug cock with the third port connected to ahousing for the syringe tip After connecting the two vessels and thesyringe to the device, the cock is positioned so as to put the syringein communication with the bottle containing the perfusional solution orwith the vial containing the injectable solution, and the solution issucked into the syringe. Then the cock is rotated so as to connect thesyringe with the bottle of medicament to be reconstituted, and theliquid is injected from the syringe in the bottle. Once diluted, themedicament is sucked from its bottle and, in the case of preparation ofproducts to be administered by infusion, the cock is rotated so as toconnect again the syringe with the bottle of perfusional solution andthe diluted medicament is transferred from the syringe to the bottle ofsolution, to give the product ready for infusion.

The last one of the 29 figures accompanying the above PCT applicationshows an embodiment which takes into account (at least in part) thatthis series of operations, carried out in a closed system, requires thepresence of some apertures for the passage of air. According to thedisclosure, one of the two spikes is provided with two internalchannels, one for the liquid and the other for the air passage, thelatter terminating in an external hydrophobic filter.

None of the solutions taught by the PCT application publ. No. WO96/29113, however, is concerned with the case where one of the twocontainers to be connected is not a bottle or a vial, rather it is aflexible bag of the kind currently employed, with increasing diffusion,for perfusional solutions. In spite of the fact that this type ofcontainers is referred to in the introduction of the application asbeing one of the three possible kinds of medicinal containers (alongwith the bottles and the ampoules), and is subsequently mentioned,generically, in the description, all of the containers shown in detailin the disclosure are rigid cylindrical vessels with pierceable rubberstopper. No specific embodiment is disclosed having a connection systemsuitable for use, in particular, with intravenous bags.

As it is known, the bags of liquid products for pharmaceutical use knownas intravenous (IV) bags are generally rectangular containers made offlexible plastic material, closed along two or more sides by heatsealing. One or, more often, two tubular elements for accessing thecontents of the bag are inserted along one edge of the bag. One of thetwo tubes is intended to be connected, in use, to the drip chamber ofthe infusion tubing, to intravenously administer to the patient thefluid contained in the bag. The other tube projecting from the bag edge,currently referred to as the injection point, is used to inject in theIV bag additional agents, such as suitably dosed drugs to be dilutedinto the perfusional solution contained in the bag. The tube of theinjection point is normally sealed at one end by a fixed cylindricalplug made of para rubber. The latter allows to introduce a syringeneedle for the injection of a drug in the IV bag and to withdraw theneedle thereafter without leaving a hole in the plug. The injectionpoint tube is often—but not always—provided with a terminal section ofgreater diameter at the point where the rubber plug is inserted. Thesize of the injection point of the IV bags currently in use is notstandardised and may range, e.g., from 8 mm to 12.5 mm in diameter (atthe point where the para rubber is inserted) and from less than 2 cm tomore than 8 cm in length.

The design of a device for connecting two medicinal containers accordingto the general teachings of the PCT application publ. No. WO 96/29113wherein one of the two containers, instead of being a conventionalbottle or vial, is a bag of the type described above appears to involvesome practical problems that have not been considered in the saiddisclosure. Such problems are mainly due to the need of providing afunctional connection and a tight fastening between the transfer deviceand the bag, specifically between the device and the tube of theinjection point. Such requirement is even more critical in view of thefact that in using the concerned device to transfer the products fromone container to the other through the syringe the assembly ofcontainers and syringe is repeatedly turned upside down. In suchoperations an IV bag containing a liquid product is clearly moredifficult to handle than a rigid bottle.

In order to overcome the foregoing problems, the present inventionprovides a device wherein one of the two opposedly placed housings forthe head of vials or bottles disclosed in the above PCT application isreplaced by a housing with fastening means suitable to enclose theinjection point tube of a bag of pharmaceutical product and to be firmlytightened around the said tube, thus preventing the bag from coming awayfrom the assembly during the handling of the device. The hollow spikeoriginally provided in the concerned housing is replaced by a steelneedle of the kind used for syringes, or else by a spike made ofplastics but capable of piercing the para rubber of the injection pointof the bag.

Therefore, the present invention specifically provides a fluid transferdevice connecting a medicinal vessel and an intravenous (IV) bag forenabling the mixing in dosed system of the two products containedtherein, comprising a three-way plug valve assembly with a first port,provided along the rotation axis of said valve, ending in a connectorfor a syringe, and a second and a third port, opposite to each other andboth orthogonal to said first port, each one provided into a respectivespike connected to a housing for a container of medicinal product, thesaid valve being so shaped as to alternatively connect said first portwith said second port or with said third port, wherein within the firstone of the said two spikes a further independent channel is provided forthe inlet and the outlet of air, communicating with the externalenvironment through a hydrophobic filter included in the device,characterised in that the second one of the said two spikes is capableof piercing the rubber closure of the injection point of a bag ofmedicinal product, and in that the housing provided on said second spikeconsists of two flexible arms attached to the device close to the pointwhere the said second spike is connected to the device, said armsextending substantially parallel to said second spike and beingfastenable to each other at the respective ends, so as to be tightenedaround the tube of the said injection point.

Further structural and functional features of the device according tothe invention are specified in the dependent claims. The said features,as well as the advantages of the invention, will be clearer withreference to a specific embodiment thereof, which is shown by way ofexample in the accompanying drawings, wherein:

FIG. 1 is a perspective view of a fluid transfer device according to theinvention;

FIG. 2 is a vertical cross-sectional view of the device of FIG. 1, withsome elements not sectioned;

FIG. 3 is a vertical cross-sectional view of the only structural frameelement of the device of FIG. 1;

FIG. 4 is a side elevation view of the same structural element of FIG.3; and

FIG. 5 is a plan view from the bottom view of the same structuralelement of FIG. 3.

As it is shown in FIGS. 1 and 2, the device according to the inventioncomprises a spike (1) capable of piercing the rubber stopper of a bottleor vial of medicament, e.g. a powder medicament to be reconstituted or amedicament in a concentrated liquid form, a second spike (2) consisting,in the embodiment shown, of a steel needle for syringes, capable ofpiercing the para rubber latex plug dosing a bag containing aperfusional solution and a three-way valve assembly (3). The plug (4) ofthe valve assembly (3) is provided with a coaxial port with a luer lockconnector (5) for a needle-less syringe.

In FIGS. 1 and 2 the valve (3) is represented in the position that putsin communication—through the hole (6), the channel (7) for the liquidflow provided within the main structural body of the device, and theneedle (2)—the syringe connected in (5) with a bag of perfusional orintravenous solution. By rotating the valve (3) by 180°, the hole (6)becomes aligned with the channel (8) for the liquid flow provided in thespike (1) connected to the medicament vial, thus putting the latter incommunication with the syringe.

In FIG. 2 only, the spike (1) and the needle (2) are represented coveredby the corresponding protection caps (9) and (10) (not sectioned), withwhich they are marketed. Also, the connector (5) for the syringe is(schematically) shown closed by a screw cap (11). Preferably, the deviceis entirely made of plastic material, except the needle; by way ofexample, the main body of the device can be made of polycarbonate andthe valve plug (4) can be made of polypropylene. It is clear that, inthe event that it is possible to produce a plastic spike capable ofpiercing the closure of the injection point of the bags of liquidproducts for intravenous infusion, the needle (2) of the device can bereplaced by a spike integral with the device, thereby resulting in adevice with the hollow tubular element (12) extending into a piercingtip.

The steel needle (2) of the device shown in the figures may be assembledto the plastic body of the device by means of a suitable adhesiveprovided on the tubular element (12), or by means of a luer lockconnector of the kind normally used in syringes, or by any other type ofthreaded coupling between the two elements. Further, the fixedconnection between the needle and the tubular element (12) of the devicemay be obtained through resilient fastening means, such as clampingmeans or clips provided on the edge of the tubular element (12).

Within the spike (1) there is provided a second channel (13) for thepassage of air, so as to allow venting of the vial connected theretoduring the transfer and mixing operations. The channel (13) iscompletely separate from the three-way valve assembly (3), andcommunicates with a hydrophobic filter (14). The filter (14) is providedwith an internal membrane (15) (visible in the sectioned part) having aporosity of 0.22 μm, suitable to prevent both the escape of aerosoltoward the exterior and the entrance of any micro organisms, which mightpenetrate in the system with the air sucked in from the atmosphere, thuspolluting the product. The filter (14) can be made, for instance, ofPVC, with a commercially available porous membrane made of a modifiedacrylic copolymer cast on a non-woven nylon support, post-treated forhydrophobicity through UV B beam polymerisation.

Since the second container attached to the device is a flexible bag, theproblem of providing a port for the passage of air also in theconnection with this container does not subsist. Actually, the IV bagadapts itself to any increase or decrease of the internal pressure bymodifying its volume.

As it is shown in FIGS. 1 and 2, and in greater detail in FIGS. 3 and 4,the spike (1) for the bottle or vial of medicament is provided with ahousing (16) for the latter, that consists of a circular plate on whichthe neck of the bottle abuts when the latter is inserted on the spike(1). The needle (2) intended to perforate the rubber plug of the IV bagis in turn provided, at the base of the tubular element (12) on which itis mounted, with a housing (17) for the injection point of the bag. Thehousing (17) consists of two flexible arms (18, 19) connected through anangular section to the main body of the device, which arms may befastened to each other at their distal ends by means of two couples oflocking arms (20, 21) opposedly placed. The locking arms (20, 21) areconnected at an angle to the distal ends of the two arms (18, 19). Thedistance between the two flexible arms (18, 19) is sufficient to forthem to enclose the terminal section of the injection point tube of allthe IV bags currently on the market, and the flexibility of the armsallows the passage of said terminal section between the two couples oflocking arms (20, 21).

Preferably, the two couples of locking arms (20, 21) have the shapeshown in detail in FIG. 5, i.e. each of them includes a coupling with anotched profile—on the arm (20)—and a co-operating tooth—on the arm(21). On each one of the locking arms (21) bearing the tooth there isprovided, at the end opposite to the said tooth, a lever projection (22)for use in disengaging the said tooth from the corresponding notchedprofile.

By means of the system with toothed profile and co-operating catch, anddue to the flexibility of the arms (18, 19) it is possible to firmlytighten the housing (17) around the injection point tube of any bag, inspite of the fact that the said tubes have variable diameter. As it ismore clearly shown in FIG. 5, to improve the grip on the tube theflexible arms (18, 19) bearing the two couples of locking arms (20, 21)both comprise, on the side facing the needle (2), a margin shaped as acircumference section, to fit the outer surface of the tube of saidinjection point.

The procedure of use of the device according to the invention is asfollows. First, the vial containing the medicament is inserted on thespike (1), the IV bag is inserted through its injection point on theneedle (2) (firmly tightening the toothed locking arms described above)and the syringe is introduced in the luer lock connector (5), with thevalve (3) opening (and, correspondingly, the valve knob) turned towardsthe IV bag and the latter in the upward position. Then, the desiredamount of liquid is sucked by means of the syringe from the bag ofsolution; further, the valve (3) is rotated towards the vial ofmedicament (which is placed in the lower position) and the solution isinjected in the vial. Subsequently, the whole assembly is turnedupside-down and the diluted drug is drawn in the syringe. At this stagethe syringe can be disconnected to provide it with a needle and injectthe diluted/reconstituted drug to the patient In the alternative, afterrotating the valve (3) knob again towards the bag of solution, thediluted/reconstituted drug is introduced in the bag for theadministration by infusion. The above overturning operations have theobject of making the liquid always flow downwards in every transferstep.

Since the diluted medicament is sucked in the syringe with the vialplaced upside-down, the corresponding spike (1) is provided, on theinlet hole of the channel (8) for the liquid passage, with aparticularly sharp cut, as it is more clearly shown in FIG. 2. Thisarrangement makes it possible to suck completely the liquid contained inthe vial without any risk of disconnecting the spike (1) from thedevice, as it may happen when the vial is lifted too much from its seatin order to drive the remaining liquid into the channel (8).

The present invention has been disclosed with particular reference tosome specific embodiments thereof, but it should be understood thatmodifications and changes may be made by the persons skilled in the artwithout departing from the scope of the invention as defined in theappended claims.

What is claimed is:
 1. A fluid transfer device connecting a medicinal vessel and an intravenous (IV) bag for enabling the mixing in closed system of the two products contained therein, comprising a three-way plug valve assembly (3) with a first port, provided along the rotation axis of said valve (3), ending in a connector (5) for a syringe, and a second and a third port (8, 7) opposite to each other and both orthogonal to said first port, each one provided into a respective spike (1, 2) connected to a housing (16, 17) for a container of medicinal product, the said valve (3) being so shaped as to alternatively connect said first port with said second port (8) or with said third port (7), wherein within the first one of the said two spikes (1) a further independent channel (13) is provided for the inlet and the outlet of air, communicating with the external environment through a hydrophobic filter (14) included in the device, characterised in that the second one of said two spikes (2) is capable of piercing the rubber closure of the injection point of a bag of medicinal product, and in that the housing (17) provided on said second spike (2) consists of two flexible arms (18, 19) attached to the device close to the point where the said second spike (2) is connected to the device, said arms (18, 19) extending substantially parallel to said second spike (2) and being fastenable to each other at the respective ends, so as to be tightened around the tube of the said injection point.
 2. Device according to claim 1, wherein the said second spike is a steel needle (2) of the kind used in syringes, connected to a hollow tubular element (12) of the device, providing the corresponding port (7).
 3. Device according to claim 1, wherein the said second spike is a hollow spike made of plastic material, constituting the extension of a hollow tubular element (12) of the device, providing the corresponding port (7).
 4. Device according to claim 1, wherein the said two flexible arms (18, 19) are connected to the device through an angular section close to the base of said second spike (2), and are fastenable to each other, at their distal ends, by means of two couples of locking arms (20, 21) opposedly placed, connected at an angle to the said distal ends.
 5. Device according to claim 4, herein each one of the said two couples of locking arms (20, 21) includes a coupling with a notched profile and a co-operating tooth.
 6. Device according to claim 5, wherein each one of the said two locking arms (21) bearing the said tooth is provided, at the end opposite to said tooth, with a lever projection (22) for use in disengaging the said tooth from the corresponding notched profile.
 7. Device according to claim 1, wherein the ends of said two flexible arms (18, 19) bearing the said two couples of locking arms (20, 21) both comprise, on the side facing said second spike (2), a margin shaped as a circumference section fitting the outer surface of the tube of said injection point. 